Impact of Fe3O4-porphyrin hybrid nanoparticles on wheat: Physiological and metabolic advance.

Iron-magnetic nanoparticles (Fe-NMPs) are widely used in environmental remediation, while porphyrin-based hybrid materials anchored to silica-coated Fe3O4-nanoparticles (Fe3O4-NPs) have been used for water disinfection purposes. To assess their safety on plants, especially concerning potential environmental release, it was investigated for the first time, the impact on plants of a silica-coated Fe3O4-NPs bearing a porphyrinic formulation (FORM) - FORM@NMP. Additionally, FORM alone and the magnetic nanoparticles without FORM anchored (NH2@NMP) were used for comparison. Wheat (Triticum aestivum L.) was chosen as a model species and was subjected to three environmentally relevant doses during germination and tiller development through root application. Morphological, physiological, and metabolic parameters were assessed. Despite a modest biomass decrease and alterations in membrane properties, no major impairments in germination or seedling development were observed. During tiller phase, both Fe3O4-NPs increased leaf length, and photosynthesis exhibited varied impacts: both Fe3O4-NPs and FORM alone increased pigments; only Fe3O4-NPs promoted gas exchange; all treatments improved the photochemical phase. Regarding oxidative stress, lipid peroxidation decreased in FORM and FORM@NMP, yet with increased O2-• in FORM@NMP; total flavonoids decreased in NH2@NMP and antioxidant enzymes declined across all materials. Phenolic profiling revealed a generalized trend towards a decrease in flavones. In conclusion, these nanoparticles can modulate wheat physiology/metabolism without apparently inducing phytotoxicity at low doses and during short-time exposure. ENVIRONMENTAL IMPLICATION: Iron-magnetic nanoparticles are widely used in environmental remediation and fertilization, besides of new applications continuously being developed, making them emerging contaminants. Soil is a major sink for these nanoparticles and their fate and potential environmental risks in ecosystems must be addressed to achieve more sustainable environmental applications. Furthermore, as the reuse of treated wastewater for agricultural irrigation is being claimed, it is of major importance to disclose the impact on crops of the nanoparticles used for wastewater decontamination, such as those proposed in this work.

Genotoxicity and heating Performance of VxFe3-xO4 nanoparticles in Health applications.

The applications of magnetic nanoparticles (MNPs) as biocatalysts in different biomedical areas have been evolved very recently. One of the main challenges in this field is to design affective MNPs surfaces with catalytically active atomic centres, while producing minimal toxicological side effects on the hosting cell or tissues. MNPs of vanadium spinel ferrite (VFe2O4) are a promising material for mimicking the action of natural enzymes in degrading harmful substrates due to the presence of active V5+ centres. However, the toxicity of this material has not been yet studied in detail enough to grant biomedical safety. In this work, we have extensively measured the structural, compositional, and magnetic properties of a series of VxFe3-xO4 spinel ferrite MNPs to assess the surface composition and oxidation state of V atoms, and also performed systematic and extensive in vitro cytotoxicity and genotoxicity testing required to assess their safety in potential clinical applications. We could establish the presence of V5+ at the particle surface even in water-based colloidal samples at pH 7, as well as different amounts of V2+ and V3+ substitution at the A and B sites of the spinel structure. All samples showed large heating efficiency with Specific Loss Power values up to 400 W/g (H0 = 30 kA/m; f = 700 kHz). Samples analysed for safety in human hepatocellular carcinoma (HepG2) cell line with up to 24h of exposure showed that these MNPs did not induce major genomic abnormalities such as micronuclei, nuclear buds, or nucleoplasmic bridges (MNIs, NBUDs, and NPBs), nor did they cause DNA double-strand breaks (DSBs) or aneugenic effects-types of damage considered most harmful to cellular genetic material. The present study is an essential step towards the use of these type of nanomaterials in any biomedical or clinical application.

Non-invasive methods of monitoring Fe3O4 magnetic nanoparticle toxicity in human liver HepaRG cells using impedance biosensing and Coherent anti-Stokes Raman spectroscopic (CARS) microscopy.

Functionalized nanoparticles have been developed for use in nanomedicines for treating life threatening diseases including various cancers. To ensure safe use of these new nanoscale reagents, various assays for biocompatibility or cytotoxicity in vitro using cell lines often serve as preliminary assessments prior to in vivo animal testing. However, many of these assays were designed for soluble, colourless materials and may not be suitable for coloured, non-transparent nanoparticles. Moreover, cell lines are not always representative of mammalian organs in vivo. In this work, we use non-invasive impedance sensing methods with organotypic human liver HepaRG cells as a model to test the toxicity of PEG-Fe3O4 magnetic nanoparticles. We also use Coherent anti-Stokes Raman Spectroscopic (CARS) microscopy to monitor the formation of lipid droplets as a parameter to the adverse effect on the HepaRG cell model. The results were also compared with two commercial testing kits (PrestoBlue and ATP) for cytotoxicity. The results suggested that the HepaRG cell model can be a more realistic model than commercial cell lines while use of impedance monitoring of Fe3O4 nanoparticles circumventing the uncertainties due to colour assays. These methods can play important roles for scientists driving towards the 3Rs principle - Replacement, Reduction and Refinement.

Comparative studies on the cytotoxic effects induced by iron oxide nanoparticles in cancerous and noncancerous human lung cells subjected to an alternating magnetic field.

The cytotoxic effects of water-based ferrofluids composed of iron oxide nanoparticles, including magnetite (Fe3O4) and maghemite (γ-Fe2O3), ranging from 15 to 100 nm, were examined on various lung cancer cells including adenocarcinomic human alveolar basal epithelial cells (A549), nonsmall lung squamous cell carcinoma (H1703), small cell lung cancer cells (DMS 114), and normal bronchial epithelial cells (BEAS-2B). The cytotoxic effect was evaluated both with and without exposure to an alternating magnetic field (AMF). The studies revealed that neither AMF nor iron oxide nanoparticles when tested individually, produced cytotoxic effects on either cancerous or noncancerous cells. However, when applied together, they led to a significant decrease in cell viability and proliferative capacity due to the enhanced effects of magnetic fluid hyperthermia (MFH). The most pronounced effects were found for maghemite (<50 nm) when subjected to an AMF. Notably, A549 cells exhibited the highest resistance to the proposed hyperthermia treatment. BEAS-2B cells demonstrated susceptibility to magnetized iron oxide nanoparticles, similar to the response observed in lung cancer cells. The studies provide evidence that MFH is a promising strategy as a standalone treatment for different types of lung cancer cells. Nevertheless, to prevent any MFH-triggered adverse effects on normal lung cells, targeted magnetic ferrofluids should be designed.

Airborne magnetite nanoparticles induced early vascular pathologies by disrupting lipid metabolism under high-fat dietary patterns.

Magnetite nanoparticles (MNPs) have been extensively detected in the atmospheric environment and implicated as a prominent threat to atherosclerosis, a chronic vascular inflammatory disease. Due to globalization and economic development, the dramatic shift in diet from traditional to high-fat dietary patterns aggravated atherosclerosis progression induced by environmental factors. However, limited knowledge is available regarding vascular risks and underlying mechanisms of airborne MNPs in high-risk populations with high-fat dietary habits. Herein, we demonstrated that MNPs exerted a proatherogenic effect under high-fat dietary patterns, leading to aortic wall thickening, elastic fiber disorganization, macrophage infiltration, and local inflammation. Based on the correlation analysis between MNPs and PM group, we identified that MNPs might be a key PM component in atherogenic toxicity. MNPs exposure disturbed the dynamic process of lipid metabolism, manifested as aortic lipid accumulation, dyslipidemia, and hepatic lipid metabolism disorder, which was modulated by the JAK-STAT pathway. Overall, these findings provide new insight into understanding the cardiovascular risks and mechanisms of MNPs among high-risk populations.

Reduced lysosomal activity and increased amyloid beta accumulation in silica-coated magnetic nanoparticles-treated microglia.

Nanoparticles have been used in neurological research in recent years because of their blood-brain barrier penetration activity. However, their potential neuronanotoxicity remains a concern. In particular, microglia, which are resident phagocytic cells, are mainly exposed to nanoparticles in the brain. We investigated the changes in lysosomal function in silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)]-treated BV2 murine microglial cells. In addition, we analyzed amyloid beta (Aß) accumulation and molecular changes through the integration of transcriptomics, proteomics, and metabolomics (triple-omics) analyses. Aß accumulation significantly increased in the 0.1 µg/µl MNPs@SiO2(RITC)-treated BV2 cells compared to the untreated control and 0.01 µg/µl MNPs@SiO2(RITC)-treated BV2 cells. Moreover, the MNPs@SiO2(RITC)-treated BV2 cells showed lysosomal swelling, a dose-dependent reduction in proteolytic activity, and an increase in lysosomal swelling- and autophagy-related protein levels. Moreover, proteasome activity decreased in the MNPs@SiO2(RITC)-treated BV2 cells, followed by a concomitant reduction in intracellular adenosine triphosphate (ATP). By employing triple-omics and a machine learning algorithm, we generated an integrated single molecular network including reactive oxygen species (ROS), autophagy, lysosomal storage disease, and amyloidosis. In silico analysis of the single triple omics network predicted an increase in ROS, suppression of autophagy, and aggravation of lysosomal storage disease and amyloidosis in the MNPs@SiO2(RITC)-treated BV2 cells. Aß accumulation and lysosomal swelling in the cells were alleviated by co-treatment with glutathione (GSH) and citrate. These findings suggest that MNPs@SiO2(RITC)-induced reduction in lysosomal activity and proteasomes can be recovered by GSH and citrate treatment. These results also highlight the relationship between nanotoxicity and Aß accumulation.

Biodistribution and histological analysis of iron oxide-dextran nanoparticles in wistar rats.

Iron oxide nanoparticles (IONP) are showing promise in many biomedical applications. One of these- magnetic hyperthermia- utilizes externally applied alternating magnetic fields and tumor-residing magnetic nanoparticles to generate localized therapeutic temperature elevations. Magnetic hyperthermia is approved in Europe to treat glioblastoma and is undergoing clinical assessment in the United States to treat prostate cancer. In this study, we performed biodistribution and histological analysis of a new IONP (RCL-01) in Wistar rats. These nanoparticles are currently undergoing clinical assessment in locally advanced pancreatic ductal adenocarcinoma to determine the feasibility of magnetic hyperthermia treatment in this disease. The study presented here aimed to determine the fate of these nanoparticles in vivo and whether this results in organ damage. Wistar rats were injected intravenously with relatively high doses of IONP (30 mgFe/kg, 45 mgFe/kg and 60 mgFe/kg) and compared to a vehicle control to determine the accumulation of iron in organs and whether this resulted in histological changes in these tissues. Dose-dependent increases of iron were observed in the liver, spleen and lungs of IONP-treated animals at 7 days postinjection; however, this did not result in significant histological changes in these tissues. Immunofluorescent imaging determined these nanoparticles are internalized by macrophages in tissue, suggesting they are readily phagocytosed by the reticuloendothelial system for eventual recycling. Notably, no changes in iron or dextran staining were found in the kidneys across all treatment groups, providing evidence for potential renal clearance.

Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety.

Introduction: One of the major challenges in the clinical translation of nanoparticles is the development of formulations combining favorable efficacy and optimal safety. In the past, iron oxide nanoparticles have been introduced as an alternative for gadolinium-containing contrast agents; however, candidates available at the time were not free from adverse effects. Methods: Following the development of a potent iron oxide-based contrast agent SPIONDex, we now performed a systematic comparison of this formulation with the conventional contrast agent ferucarbotran and with ferumoxytol, taking into consideration their physicochemical characteristics, bio- and hemocompatibility in vitro and in vivo, as well as their liver imaging properties in rats. Results: The results demonstrated superior in vitro cyto-, hemo- and immunocompatibility of SPIONDex in comparison to the other two formulations. Intravenous administration of ferucarbotran or ferumoxytol induced strong complement activation-related pseudoallergy in pigs. In contrast, SPIONDex did not elicit any hypersensitivity reactions in the experimental animals. In a rat model, comparable liver imaging properties, but a faster clearance was demonstrated for SPIONDex. Conclusion: The results indicate that SPIONDex possess an exceptional safety compared to the other two formulations, making them a promising candidate for further clinical translation.

Removal of lithium from aqueous solutions by solid-phase extraction using sawdust loaded with magnetite nanoparticles and study of apoptosis, MDA and 8-OHdG caused by lithium toxicity in fish brain.

Lithium, which has a high industrial value, is an environmental pollutant of concern to those who work with lithium in industry as well as to the general public. Biological parameters such as MDA, 8-OHdG, apoptosis (caspase-3), and acetylcholinesterase (AChE) were studied to determine the toxic effects on the brain tissue of the model organism (Carassius auratus) exposed to high dose lithium. According to the results obtained, it was found that lithium exposure caused oxidative stress with an increase in MDA level over time and, accordingly, DNA damage and apoptosis occured in brain tissue. It was also found that a decrease in AChE activity was observed, and the high levels of MDA, 8-OHdG, and caspase-3 activity obtained in brain tissue supported this result. The solid phase extraction (SPE) method was used to effectively remove lithium, which has unfavorable effects on living organisms, from aqueous solutions. In this method, a sawdust loaded with magnetite nanoparticles (MNLS) was prepared as an adsorbent for solid phase extraction by a simple method, and it was characterized. Optimal conditions for the SPE process were defined and it was found that lithium could be removed from solution onto the MNLS surface with a high yield of about 96%. The results of the study are crucial for proposing a simple and applicable high performance method.

Influence of PEG Chain Length of Functionalized Magnetic Nanoparticles on the Cytocompatibility and Immune Competence of Primary Murine Macrophages and Dendritic Cells.

A major drawback of nanoparticles (NPs) for biomedical applications is their preferential phagocytosis in immune cells, which can be avoided by surface modifications like PEGylation. Nevertheless, examinations of different polyethylene glycol (PEG) chain lengths on the competence of immune cells as well as possible immunotoxic effects are still sparse. Therefore, primary murine macrophages and dendritic cells were generated and incubated with magnetic nanoporous silica nanoparticles (MNPSNPs) modified with different mPEG chains (2 kDa, 5 kDa, and 10 kDa). Cytotoxicity, cytokine release, and the formation of reactive oxygen species (ROS) were determined. Immune competence of both cell types was examined and uptake of MNPSNPs into macrophages was visualized. Concentrations up to 150 µg/mL MNPSNPs showed no effects on the metabolic activity or immune competence of both cell types. However, ROS significantly increased in macrophages incubated with larger PEG chains, while the concentration of cytokines (TNF-α and IL-6) did not indicate a proinflammatory process. Investigations on the uptake of MNPSNPs revealed no differences in the onset of internalization and the intensity of intracellular fluorescence. The study gives no indication for an immunotoxic effect of PEGylated MNPSNPs. Nevertheless, there is still a need for optimization regarding their internalization to ensure an efficient drug delivery.

Functionalized Magnetite Nanoparticles: Characterization, Bioeffects, and Role of Reactive Oxygen Species in Unicellular and Enzymatic Systems.

The current study evaluates the role of reactive oxygen species (ROS) in bioeffects of magnetite nanoparticles (MNPs), such as bare (Fe3O4), humic acids (Fe3O4-HA), and 3-aminopropyltriethoxysilane (Fe3O4-APTES) modified MNPs. Mössbauer spectroscopy was used to identify the local surrounding for Fe atom/ions and the depth of modification for MNPs. It was found that the Fe3O4-HA MNPs contain the smallest, whereas the Fe3O4-APTES MNPs contain the largest amount of Fe2+ ions. Bioluminescent cellular and enzymatic assays were applied to monitor the toxicity and anti-(pro-)oxidant activity of MNPs. The contents of ROS were determined by a chemiluminescence luminol assay evaluating the correlations with toxicity/anti-(pro-)oxidant coefficients. Toxic effects of modified MNPs were found at higher concentrations (>10−2 g/L); they were related to ROS storage in bacterial suspensions. MNPs stimulated ROS production by the bacteria in a wide concentration range (10−15−1 g/L). Under the conditions of model oxidative stress and higher concentrations of MNPs (>10−4 g/L), the bacterial bioassay revealed prooxidant activity of all three MNP types, with corresponding decay of ROS content. Bioluminescence enzymatic assay did not show any sensitivity to MNPs, with negligible change in ROS content. The results clearly indicate that cell-membrane processes are responsible for the bioeffects and bacterial ROS generation, confirming the ferroptosis phenomenon based on iron-initiated cell-membrane lipid peroxidation.

Synthesis and Characterization of a Biocompatible Nanoplatform Based on Silica-Embedded SPIONs Functionalized with Polydopamine.

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained increasing interest in nanomedicine, but most of those that have entered the clinical trials have been withdrawn due to toxicity concerns. Therefore, there is an urgent need to design low-risk and biocompatible SPION formulations. In this work, we present an original safe-by-design nanoplatform made of silica nanoparticles loaded with SPIONs and decorated with polydopamine (SPIONs@SiO2-PDA) and the study of its biocompatibility performance by an ad hoc thorough in vitro to in vivo nanotoxicological methodology. The results indicate that the SPIONs@SiO2-PDA have excellent colloidal stability in serum-supplemented culture media, even after long-term (24 h) exposure, showing no cytotoxic or genotoxic effects in vitro and ex vivo. Physiological responses, evaluated in vivo using Caenorhabditis elegans as the animal model, showed no impact on fertility and embryonic viability, induction of an oxidative stress response, and a mild impact on animal locomotion. These tests indicate that the synergistic combination of the silica matrix and PDA coating we developed effectively protects the SPIONs, providing enhanced colloidal stability and excellent biocompatibility.

Influence of magnetic nanoparticle biotransformation on contrasting efficiency and iron metabolism.

Magnetic nanoparticles are widely used in biomedicine for MRI imaging and anemia treatment. The aging of these nanomaterials in vivo may lead to gradual diminishing of their contrast properties and inducing toxicity. Here, we describe observation of the full lifecycle of 40-nm magnetic particles from their injection to the complete degradation in vivo and associated impact on the organism. We found that in 2 h the nanoparticles were eliminated from the bloodstream, but their initial biodistribution changed over time. In 1 week, a major part of the nanoparticles was transferred to the liver and spleen, where they degraded with a half-life of 21 days. MRI and a magnetic spectral approach revealed preservation of contrast in these organs for more than 1 month. The particle degradation led to the increased number of red blood cells and blood hemoglobin level due to released iron without causing any toxicity in tissues. We also observed an increase in gene expression level of Fe-associated proteins such as transferrin, DMT1, and ferroportin in the liver in response to the iron particle degradation. A deeper understanding of the organism response to the particle degradation can bring new directions to the field of MRI contrast agent design.

In vitro and in vivo acute toxicity of a novel citrate-coated magnetite nanoparticle.

Magnetic nanoparticles (MNps) have become powerful tools for multiple biomedical applications such as hyperthermia drivers, magnetic resonance imaging (MRI) vectors, as well as drug-delivery systems. However, their toxic effects on human health have not yet been fully elucidated, especially in view of their great diversity of surface modifications and functionalizations. Citrate-coating of MNps often results in increased hydrophilicity, which may positively impact their performance as drug-delivery systems. Nonetheless, the consequences on the intrinsic toxicity of such MNps are unpredictable. Herein, novel magnetite (Fe3O4) nanoparticles covered with citrate were synthesized and their potential intrinsic acute toxic effects were investigated using in vitro and in vivo models. The proposed synthetic pathway turned out to be simple, quick, inexpensive, and reproducible. Concerning toxicity risk assessment, these citrate-coated iron oxide nanoparticles (IONps) did not affect the in vitro viability of different cell lines (HaCaT and HepG2). Moreover, the in vivo acute dose assay (OECD test guideline #425) showed no alterations in clinical parameters, relevant biochemical variables, or morphological aspects of vital organs (such as brain, liver, lung and kidney). Iron concentrations were slightly increased in the liver, as shown by Graphite Furnace Atomic Absorption Spectrometry and Perls Prussian Blue Staining assays, but this finding was considered non-adverse, given the absence of accompanying functional/clinical repercussions. In conclusion, this study reports on the development of a simple, fast and reproducible method to obtain citrate-coated IONps with promising safety features, which may be used as a drug nanodelivery system in the short run. (263 words).

Assessment of the potential toxic effect of magnetite nanoparticles on the male reproductive system based on immunological and molecular studies.

Magnetite nanoparticles (MNPs) are the most conventional type of iron oxide nanoparticles used in the food industrial processes, removal of heavy metals, and biomedical applications in vivo or in vitro. Until now, there is no sufficient information that can confirm its effect on the body's immune system and reproductive health in males. The purpose of this research is to estimate the immunotoxic and reproductive toxic effects of MNPs in male rats. This study included 36 adult male albino rats divided into three groups. The experimental groups were intraperitoneally injected with MNPs at doses of 5 and 10 mg/kg body weight 3 times/week for 60 days, while the control group was injected with saline solution. MNPs caused a significant decrease in the body weight change of the high-treated group. MNPs produced changes in the lymphocyte proliferation rate which referred to a significant immunotoxic effect measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide reduction method. The testicular tissue of male-treated rats showed some moderate and severe degenerative changes. The sperm parameters of count, motility, and viability were significantly decreased. Sperm morphological abnormalities were detected in all treated animals. MNPs produced a significant decrease in testosterone levels, increased the level of malondialdehyde, impaired the activity of the antioxidant enzymes and induced testicular DNA damage. In conclusion, MNPs affected the normal immune state in male rats and facilitated the generation of reactive oxygen species subsequently triggering testicular oxidative stress damages. All these consequences had a negative impact on male reproductive health.

Ecotoxicological assessment of magnetite and magnetite/Ag nanoparticles on terrestrial and aquatic biota from different trophic levels.

The aim of the study is an ecotoxicological assessment of magnetite iron oxide-based nanoparticles (NPs), which have risen in popularity in the last decade, on selected terrestrial and aquatic organisms from various levels of the food chain. In the presented study various organisms, from both the terrestrial and aquatic environment, were used as targets for the assessment of NPs ecotoxicity. Plants (radish, oat), marine bacteria (A. fischeri) and crustacean (H. incongruens) were used to represent producers, decomposers, and consumers, respectively. It was found that examined NPs were harmful (to a different degree) to biota from three different trophic levels. Physicochemical characterization (size/morphology, crystallinity, composition, and magnetic properties) of the tested nanoparticles was performed by: transmission electron microscopy, X-ray diffraction, energy dispersive spectroscopy, and Mossbauer spectroscopy, respectively. Phytotoxicity was evaluated according to the OECD 208 Guideline, while acute and chronic toxicity of NPs was conducted using bioassays employing bacteria and crustacea, respectively. The phytotoxicity of all investigated iron oxide-based NPs was dependent on concentration and type of NPs formulation and was measured via biomass, seed germination, root length, shoot height, and content of plant pigments. Increasing the concentration of NPs increased phytotoxicity and mortality of aquatic organisms. Ecotoxicity of iron oxide/silver was dependent on the size and content of silver. Iron oxide NPs coated with nanosilver in a percentage ratio of 69/31 were found to be the most toxic on tested terrestrial and aquatic biota.

In Vivo Multimodal Imaging of Stem Cells Using Nanohybrid Particles Incorporating Quantum Dots and Magnetic Nanoparticles.

The diagnosis of the dynamics, accumulation, and engraftment of transplanted stem cells in vivo is essential for ensuring the safety and the maximum therapeutic effect of regenerative medicine. However, in vivo imaging technologies for detecting transplanted stem cells are not sufficient at present. We developed nanohybrid particles composed of dendron-baring lipids having two unsaturated bonds (DLU2) molecules, quantum dots (QDs), and magnetic nanoparticles in order to diagnose the dynamics, accumulation, and engraftment of transplanted stem cells, and then addressed the labeling and in vivo fluorescence and magnetic resonance (MR) imaging of stem cells using the nanohybrid particles (DLU2-NPs). Five kinds of DLU2-NPs (DLU2-NPs-1-5) composed of different concentrations of DLU2 molecules, QDs525, QDs605, QDs705, and ATDM were prepared. Adipose tissue-derived stem cells (ASCs) were labeled with DLU2-NPs for 4 h incubation, no cytotoxicity or marked effect on the proliferation ability was observed in ASCs labeled with DLU2-NPs (640- or 320-fold diluted). ASCs labeled with DLU2-NPs (640-fold diluted) were transplanted subcutaneously onto the backs of mice, and the labeled ASCs could be imaged with good contrast using in vivo fluorescence and an MR imaging system. DLU2-NPs may be useful for in vivo multimodal imaging of transplanted stem cells.

The Foam Cell Formation Associated With Imbalanced Cholesterol Homeostasis Due to Airborne Magnetite Nanoparticles Exposure.

Fine particulate matter (PM) is a leading environmental cause for the increased morbidity and mortality of atherosclerosis (AS) worldwide, but little is known about the toxic component and disturbance of PM exposure on foam cell formation, a crucial pathological process in AS. Airborne magnetite nanoparticles (NPs) have been reported to be detected in human serum, which inevitably encounter with macrophages in atherosclerotic plaques, thus throwing potential disturbance on the formation of macrophage-derived foam cells. Here we comprehensively unveiled that the environmental concentrations of PM exposure triggered and potentiated the formation of macrophage-derived foam cells using both real-ambient PM-exposed mice and AS mice models, including high-fat diet-fed mice and apolipoprotein E-deficient mice. The in vitro model further defined the dose-dependent response of PM treatment on foam cell formation. Interestingly, airborne magnetite NPs rather than nonmagnetic NPs at the same concentration were demonstrated to be the key toxic component of PM in the promoted foam cell formation. Furthermore, magnetite NPs exposure led to abnormal cholesterol accumulation in macrophages, which was attributed to the attenuation of cholesterol efflux and enhancement of lipoprotein uptake, but independent of cholesterol esterification. The in-depth data revealed that magnetite NPs accelerated the protein ubiquitination and subsequent degradation of SR-B1, a crucial transporter of cholesterol efflux. Collectively, these findings for the first time identified magnetite NPs as one key toxic component of PM-promoted foam cell formation, and provided new insight of abnormal cholesterol metabolism into the pathogenesis of PM-induced AS.

The nanotoxicity assessment of cube-like iron nitride magnetic nanoparticles at the organismal level of nematode Caenorhabditis elegans.

Magnetic nanoparticles (NPs) are suitable candidates for various medical and biological applications, despite some concerns that they may have negative impacts on human health. In this study, the toxicity effects of magnetic NPs consisting of α"-Fe16N2 captured and bioaccumulated by the nematode Caenorhabditis elegans (C. elegans) in the early larval stage are evaluated. The choice of α"-Fe16N2 NPs is based on their good structural stability when stored in saline solution and high magnetic performance. The uptake and bioaccumulation of α"-Fe16N2 NPs in intestinal cells of C. elegans was evidenced by transmission electron microscopy. After exposure to NPs up to 40 mg mL-1, C. elegans larval development, survival, feeding behavior, defecation cycles, movement and reproduction were monitored. C. elegans survival and other monitored behavioral evolutions do not show significant changes, except for a slight statistical reduction in the reproductive profile. Therefore, the present results are promising and very encouraging for investigations of applications of α"-Fe16N2 NPs in the biomedical area.

Ultrasound assisted chitosan coated iron oxide nanoparticles: Influence of ultrasonic irradiation on the crystallinity, stability, toxicity and magnetization of the functionalized nanoparticles.

Due to unique reaction conditions of the acoustic cavitation process, ultrasound-assisted synthesis of nanoparticles has attracted increased research attention. In this study, we demonstrate the effect of ultrasonic irradiation on the crystallinity, stability, biocompatibility, and magnetic properties of chitosan-coated superparamagnetic iron oxide nanoparticles (CS-SPIONs). CS solution and colloidal suspension of SPIONs were mixed and sonicated using an ultrasonic probe of 1.3 cm tip size horn, frequency (20 kHz), and power (750 W). Different samples were sonicated for 1.5, 5, and 10 min with corresponding acoustic powers of 67, 40 and 36 W, and the samples were denoted S1.5, S5, and S10, respectively. The samples were characterized using X-ray diffractometer (XRD), Energy dispersive X-ray (EDX), Transmission electronic microscope (TEM), Fourier transform infrared spectroscopy (FTIR), Zeta sizer, and vibrating sample magnetometer (VSM). Cell cytotoxicity and cell uptake were investigated with human embryonic kidney 293 (HEK-293) cells through MTT assay and Prussian blue staining, respectively. The sharp peaks of the XRD pattern were disappearing with an increase in the sonication period but a decrease in acoustic power. EDX analysis also demonstrates that atomic and weight percentages of the various elements in the samples were decreasing with an increase in the sonication period. However, the Zeta potential (ζ) values increase with an increase in the sonication period.The saturation magnetization (Ms) of the S1.5 before and after the coating is 62.95 and 86.93 emu/g, respectively. Cell cytotoxicity and uptake of the S1.5 show that above 70% of cells were viable at the highest concentration and the longest incubation duration. Importantly, the CS-SPIONs synthesized by the sonochemical method are non-toxic and biocompatible.